BackgroundIn Latin America, Peru has the second highest number of cases of monkeypox (Mpox), of which more than 50 % are Human Immunodeficiency Virus (HIV)-positive. Here, we compared the epidemiological and clinical characteristics of Mpox between people with and without HIV in Peru. MethodsWe conducted a national retrospective study using data on confirmed cases of Mpox reported by the Peruvian National Surveillance System from 15 June 2022 to 31 December 2023. ResultsA total of 3561 confirmed cases of Mpox were included. Of these, 2123 (60 %) patients were people living with HIV (PLWH), with increased odds for those aged 30 years or older, homosexual (adjusted odds ratio [aOR] 8.58 [6.95–10.59], p<0.0001), bisexual (aOR=4.44 [3.46–5.69], p<0.0001), sex workers (aOR=2.24 [1.07–4.68], p=0.032), people with a history of syphilis (aOR=2.07 [1.66–2.58], p<0.001), and hospitalized (aOR=3.08 [2.03–4.68], p<0.001). PLWH were more likely to have proctitis (aOR=1.73 [1.26–2.37], p=0.001). The overall mortality was 20 of 3561 (0.56 %). Among PLWH and Mpox, more deaths occurred in hospitalized (p<0.001) and non-ART (p<0.001) individuals. ConclusionOur findings highlight that HIV infection among Mpox cases in Peru is associated with high-risk sexual behaviour and a high likelihood of hospitalization.